RT Journal Article
T1 Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype.
A1 Chen, Lubin
A1 Wimalasena, Nivanthika K
A1 Shim, Jaehoon
A1 Han, Chongyang
A1 Lee, Seong-Il
A1 Gonzalez-Cano, Rafael
A1 Estacion, Mark
A1 Faber, Catharina G
A1 Lauria, Giuseppe
A1 Dib-Hajj, Sulayman D
A1 Woolf, Clifford J
A1 Waxman, Stephen G
AB Small-fiber neuropathy (SFN), characterized by distal unmyelinated or thinly myelinated fiber loss, produces a combination of sensory dysfunction and neuropathic pain. Gain-of-function variants in the sodium channel Nav1.7 that produce dorsal root ganglion (DRG) neuron hyperexcitability are present in 5% to 10% of patients with idiopathic painful SFN. We created 2 independent knock-in mouse lines carrying the Nav1.7 I228M gain-of-function variant, found in idiopathic SFN. Whole-cell patch-clamp and multielectrode array recordings show that Nav1.7 I228M knock-in DRG neurons are hyperexcitable compared with wild-type littermate-control neurons, but despite this, Nav1.7 I228M mice do not display mechanical or thermal hyperalgesia or intraepidermal nerve fiber loss in vivo. Therefore, although these 2 Nav1.7 I228M knock-in mouse lines recapitulate the DRG neuron hyperexcitability associated with gain-of-function mutations in Nav1.7, they do not recapitulate the pain or neuropathy phenotypes seen in patients. We suggest that the relationship between hyperexcitability in sensory neurons and the pain experienced by these patients may be more complex than previously appreciated and highlights the challenges in modelling channelopathy pain disorders in mice.
YR 2021
FD 2021
LK https://hdl.handle.net/10668/27126
UL https://hdl.handle.net/10668/27126
LA en
DS RISalud
RD Apr 17, 2025